High-throughput screening (NTS) is a means of rapidly assessing the ability of hundreds of thousands of chemical compounds to affect biological systems for the purpose of accelerating medical research. We propose an HTS core the goal of which is to enable Gl SPORE investigators to discover chemical tools to promote better understanding of colorectal cancer physiology and potentially to help reveal novel targets and therapeutic opportunities. Using state-of-the-art HTS technologies and working with Gl SPORE investigators, the Vanderbilt Institute of Chemical Biology's HTS facility has developed and validated HTS-compatible assays aimed at discovering chemical tools relevant to: 1) E-cadherin regulation in the human colon cancer cell line, SW620; 2) axin and (3-catenin stability in a novel in vitro assay system; and 3) p120's role in modulating E-cadherin activity and adherens junction formation in the Colo205 cell line. We present data demonstrating our ability to perform the HTS assays, discover compounds that affect the systems noted above, and we detail our plans to use the products of the HTS to further the aims of the Gl SPORE.